Central tolerance

Central tolerance encompasses the mechanisms that render newly developing lymphocytes in primary lymphoid organs tolerant to self antigens. Developing B cells and T cells that react strongly to self antigens either undergo alteration of their antigen receptors, or face functional inactivation, deletion by apoptosis or programming into a suppressive phenotype.

Latest Research and Reviews

  • Research | | open

    Autoreactive T cells are deleted in the thymus via thymic negative selection and Bim-mediated apoptosis. Here the authors identify a cis-acting enhancer, EBAB, that is essential for proper Bim expression and apoptosis induction, and show that EBAB deficiency specifically impairs thymic negative selection without affecting peripheral T cell homeostasis.

    • Miki Arai Hojo
    • , Kyoko Masuda
    • , Hiroaki Hojo
    • , Yosuke Nagahata
    • , Keiko Yasuda
    • , Daiya Ohara
    • , Yusuke Takeuchi
    • , Keiji Hirota
    • , Yutaka Suzuki
    • , Hiroshi Kawamoto
    •  & Shinpei Kawaoka
  • Research | | open

    Both thymic epithelial cells and dendritic cells present self antigens in the thymus to mediate thymic selection and T cell tolerance. Here the authors quantify, using two-photon live imaging of mouse thymic slices, the relative contribution of these two cell types, as well as the effects of antigen cross-presentation by dendritic cells, during tolerance induction.

    • J. N. Lancaster
    • , H. M. Thyagarajan
    • , J. Srinivasan
    • , Y. Li
    • , Z. Hu
    •  & L. I. R. Ehrlich
  • Research | | open

    The inhibitory receptor, FcγRIIb, is reported to limit autoimmune B cell response. Here the authors show that FcγRIIb has a dual role in both human and mouse, with reduced FcγRIIb expression or function associated with enhanced pre-immune B cell tolerance, yet defective control of mature autoreactive B cells in the germinal center.

    • Marion Espéli
    • , Rachael Bashford-Rogers
    • , John M. Sowerby
    • , Nagham Alouche
    • , Limy Wong
    • , Alice E. Denton
    • , Michelle A. Linterman
    •  & Kenneth G. C. Smith
  • Reviews |

    In this Review, Handel and colleagues examine the contribution of thymic T cell selection to CNS autoimmune conditions and consider how a better understanding of this contribution could lead to novel therapeutic strategies for these conditions.

    • Adam E. Handel
    • , Sarosh R. Irani
    •  & Georg A. Holländer
  • Research |

    Zhu and colleagues show that negative-selection ligands induce cooperative TCR–pMHC–CD8 trimolecular ‘catch bonds’, whereas positive-selection ligands induce TCR–pMHC and pMHC–CD8 bimolecular ‘slip bonds’.

    • Jinsung Hong
    • , Chenghao Ge
    • , Prithiviraj Jothikumar
    • , Zhou Yuan
    • , Baoyu Liu
    • , Ke Bai
    • , Kaitao Li
    • , William Rittase
    • , Miho Shinzawa
    • , Yun Zhang
    • , Amy Palin
    • , Paul Love
    • , Xinhua Yu
    • , Khalid Salaita
    • , Brian D. Evavold
    • , Alfred Singer
    •  & Cheng Zhu
    Nature Immunology 19, 1379-1390
  • Research |

    A comprehensive characterization of the thymic stroma identifies a tuft-cell-like thymic epithelial cell population that is critical for shaping the immune niche in the thymus.

    • Chamutal Bornstein
    • , Shir Nevo
    • , Amir Giladi
    • , Noam Kadouri
    • , Marie Pouzolles
    • , François Gerbe
    • , Eyal David
    • , Alice Machado
    • , Anna Chuprin
    • , Beáta Tóth
    • , Ori Goldberg
    • , Shalev Itzkovitz
    • , Naomi Taylor
    • , Philippe Jay
    • , Valérie S. Zimmermann
    • , Jakub Abramson
    •  & Ido Amit
    Nature 559, 622-626

News and Comment

  • Comments and Opinion |

    Numerous exciting studies that advanced our understanding of immune-mediated kidney disease were published in 2018. Whereas most of these studies analysed the role of pro-inflammatory mediators, several novel anti-inflammatory mechanisms were discovered that involve immune cells and mediators with previously unrecognized protective roles in renal disease.

    • Christian Kurts
    •  & Catherine Meyer-Schwesinger
  • Research Highlights |

    Two papers published in Nature introduce a new subset of medullary thymic epithelial cells with properties similar to intestinal tuft cells, including IL-25 production and chemosensing ability.

    • Kirsty Minton
  • News and Views |

    Caveolin-1 has a critical role in orchestrating the membrane organization of B cells. In its absence, signaling via the B cell antigen receptor and B cell tolerance are impaired, which results in autoimmunity.

    • Julie Zikherman
    •  & Clifford A Lowell
    Nature Immunology 18, 1065-1066
  • News and Views |

    The thymic development of CD8+ T cells requires the presentation of different sets of peptides on major histocompatibility complex class I for positive selection and negative selection.

    • Joanna Brzostek
    •  & Nicholas R J Gascoigne
    Nature Immunology 17, 896-898